Deoxycytidine kinase (dCK) is an enzyme which plays a crucial role in role in cellular divisional and which functions in the phosphorylation of several deoxyribonucleosides and their nucleoside analogs. Deoxycytidine kinase is observed to be predominantly expressed in hematopoietic tissues and is upregulated in certain solid tumors. Interestingly, dCK deficiency is also associated with certain forms of resistance to antiviral and anticancer chemotherapeutic agents. dCK is a clinically important polypeptide target because of, for example, its role in cellular divisional, as well as its association with drug resistance and/or drug sensitivity. Compounds and compositions that bind to and inhibit dCK activities in vivo are desirable for the treatment of diseases and disorders where dCK activity is implicated.
By monitoring aspects of immune function throughout the body of a patient, medical practitioners can significantly impact the diagnosis and treatment of pathological conditions including immunological disorders. Positron Emission Tomography (PET) is one example of a molecular imaging modality with numerous applications in cancer and other diseases. Positron Emission Tomography, for example, enables the measurements of molecular and cellular mechanisms throughout the body in preclinical and clinical settings. Such measurements have widespread diagnostic utility and their use for evaluation of treatment responses and to assist drug development is expanding rapidly. Studies have demonstrated the feasibility of using PET to visualize immune responses and, for example, shown that anti-tumor T cell immunity can be monitored using PET reporter gene imaging. Similar approaches may enable evaluation of T cell trafficking thus expanding their use in patients undergoing cancer immunotherapy. PET studies of immune function have been limited by a lack of specialized probes. In this context, development of probes that allow for direct measurements of immune function will significantly widen the utility of PET imaging. Compounds that bind polypeptides involved in nucleoside metabolism such as deoxycytidine kinase may find use in therapeutic methods that involve the inhibition of nucleoside metabolism as well as in imaging methods that aid the evaluation and development of therapeutic agents that inhibit polypeptides involved in nucleoside metabolism such as dCK.